Low-Dose Intradermal Flu Shots May Be Effective Vaccination

February 9, 2021
Kevin Kunzmann

A meta-analysis review suggests intradermal flu vaccines at lower doses could provide as much immunogenicity as standard intramuscular doses.

Reduced-dose influenza (flu) vaccine, administered via intradermal injection, may be a feasible and effective alternative to standard single-dose intramuscular vaccination, according to new research.

In a systematic review and meta-analysis of 30 studies relevant to vaccinating for H1N1, H3N2, and B strains of the flu, a team of Canadian investigators observed that low-dose intradermal flu vaccine does not provide a low seroconversion rate than the commonly provided 15 mcg intramuscular doses.

Intradermal vaccination is believed to possibly provide dose-sparing effects, which leads to the idea that smaller doses may provide sufficient antigenic response equivalent to intramuscular doses.

“This is physiologically plausible because the dermis is rich in Langerhans cells, dendritic cells that are very potent antigen-presenting cells capable of eliciting both cell-mediated and humoral immune responses via antigen presentation to CD4+ and CD8+ T cells, and eventual B cell activation to produce high levels of antigen-specific antibodies,” investigators wrote.

The new findings would indicate a potential dose-sparing methodology for vaccinating against the flu, an infectious disease which commonly results in up to 5 million severe illnesses and 500,000 deaths annually.

Led by Oluwaseun Egunsola, PhD, of the Department of Community Health Services, University of Calgary Alberta, investigators extracted data from relevant studies published between 2010 and June 5, 2020. Relevant studies observed immunogenicity or safety of intradermal and intramuscular flu vaccinations across all age groups.

Egunsola sought primary outcomes including geometric mean titer, seroconversion, seroprotection, and adverse events associated with either vaccine dosing strategy.

The analysis included 30 relevant studies, including 29 randomized clinical trials with 13,750 total participants, and a cohort study of 164,201 participants.

Investigators observed no statistically significant difference in seroconversion rates between 3-mcg, 6-mcg, 7.5-mcg, and 9-mgc intradermal flu vaccine doses and the 15-mcg intramuscular vaccine doses across the H1N1, H3N2, and B strains.

However, they did observe significantly higher rates with the 15-mcg intradermal dose compared with the equivalent intramuscular dose for the H1N1 strain (rate ratio [RR], 1.10; 95% CI, 1.01-1.20) and B strain (RR, 1.40; 95% CI, 1.13 – 1.73).

Seroprotection rates for the 9-mcg and 15-mcg intradermal doses did not significantly vary from the 15-mcg intramuscular dose for all flu strains, aside from the 15-mcg intradermal dose rates being significantly higher for the H1N1 strain.

Intradermal doses were associated with significantly greater local adverse events than the 15-mcg intramuscular dose, however, particularly for rates of erythemia and swelling. Only the 9-mcg intradermal dose was associated with greater risk of fever and chills than the intramuscular dose.

Nonetheless, investigators observed key immunogenicity was delivered similarly from all observed doses of intradermal flu vaccination as it is from 15-mcg intramuscular doses—and was even bettered by the full-dose (15 mcg) intradermal dose, suggesting a dose-related immunological response rate by the intradermal method.

They wrote it is reasonable to infer the low-dose intradermal vaccine could be an alternative to the standard flu vaccination dose, pending further research.

“It will be important to determine if this dose-sparing finding holds true across age groups and for newer vaccines, particularly when recent high-dose formulations have demonstrated improved immunogenicity in older adults in whom immune responses have historically struggled,” they concluded.

The study, “Immunogenicity and Safety of Reduced-Dose Intradermal vs Intramuscular Influenza Vaccines,” was published online in JAMA Network Open.